Rheumatoid arthritis is a chronic inflammatory disease primary affecting peripheral synovial joints. The etiopathogenesis of rheumatoid arthritis appears to be multi-factorial, including hereditary susceptibility, postnatal events in immune maturation, repeated exposure to environmental antigens and amplifying cytokine networks that perpetuate inflammation. The causative antigens may be directly expressed at the site of immune attack pr be cross reactive with antigenic epitopes naturally occurring in the joint. We postulate that stimulating a subset of T cells that respond to a joint specific antigen to secrete IL4 or IL10 by manipulating the antigen presenting environment may abrogate disease. In our preliminary experiments we have developed a system whereby limited epitopes are expressed by plasmid DNA injected into the dermis or muscle tissues of mice. The T cell response to these antigens is additionally biased not only by the epitope expressed, but also by different co-stimulatory molecules expressed in the vicinity. This method of providing different elements involved in priming of an immune response creates a local immunologic window. In our laboratory we have also developed a unique system to limit antigen presentation to an isoform of CD1. We aim to 1) assess the effects of different co-stimulatory molecules on deviating the immune response to collagen 2) determine if providing additional antigenic chaperones or covalently linking the antigen chaperones potentiates immune deviation 3) evaluate a regulatory role for the CD1D1 restricted responses in collagen induced arthritis and 4) determine if the findings form our three strategies in the collagen induced arthritis model apply to a different transgenic mouse model in which the mice spontaneously develop arthritis.